New diabetes pill seen as risky

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A new diabetes pill that appeared headed for federal approval can double the risk of heart attack, stroke and death, according to analysts at the Cleveland Clinic, whose independent findings were rushed online yesterday because of public safety concerns.

Last month, the drug in question, muraglitazar, was recommended for approval by an advisory panel to the Food and Drug Administration (FDA) by an 8-1 vote. And on Tuesday, the drug's manufacturers announced the FDA had told them muraglitazar was "approvable" but had requested additional safety information.

But in reviewing the same data examined by the FDA's advisory panel, Cleveland Clinic cardiovascular specialists found that the combined incidence of death, heart attack and stroke was 2.23 times greater in diabetics given muraglitazar than in those given either a similar drug or a placebo.

In those taking muraglitazar, heart attacks or strokes occurred in 35 of 2,374 patients. There were nine such events in 1,351 patients on a dummy pill or another diabetes medication.

"Relative risk is what tells you if a drug is hazardous. This one shows a doubling of risk. The advisory panel was asleep at the switch. They did not give good information to the FDA," said Dr. Steven Nissen, medical director of the Cleveland Clinic's Cardiovascular Coordinating Center.

Dr. Nissen and two colleagues at the clinic were authors of the online report in the Journal of the American Medical Association (JAMA), which recommends against quick approval of the therapy that is meant to improve cholesterol and lipid levels and control blood-sugar levels in type 2 diabetics.

Type 2 diabetes is the most common form of the disease, affecting at least 16 million Americans, many of whom are overweight adults.

"We wanted to avoid the kind of experience we went through with Vioxx," Dr. Nissen said yesterday.

A year ago, Vioxx, a popular arthritis painkiller, was voluntarily withdrawn from the market by Merck & Co. after a study showed that the drug nearly doubled the risk of stroke among people taking it for at least 18 months.

Dr. Nissen noted that in August 2001, he and Dr. Eric Topol, another author of the new online JAMA report, had another study published in the medical journal linking Vioxx to cardiovascular risks. "But in that case, we couldn't stop the freight train," he said.

Merck and another pharmaceutical giant, Bristol-Myers Squibb, are the makers of the experimental diabetes pill, whose trade name will be Paragluva if it goes on the market.

In a joint statement yesterday, the companies said they are "eager to begin discussions with the FDA to address more fully the cardiovascular safety profile of the compound and to determine what additional information may be necessary."

Dr. Nissen yesterday praised the editors of JAMA for treating his concerns about muraglitazar as a "public health emergency" and rushing them into print.